Secondary primary malignancies after CD-19 directed CAR-T-cell therapy in lymphomas: A report from the Italian CART-SIE study.

Secondary primary malignancies (SPM) have been reported after anti-BCMA or anti-CD19 chimeric antigen receptor (CAR)-T-cell therapies. While the cytotoxic effect of antecedent therapies, including chemotherapy and radiotherapy, has been well established, few data are available on risk related to CAR-T immunotherapies. The study aimed to analyse the incidence of SPM in 651 patients enrolled in the Italian prospective observational CART-SIE study. SPMs were documented in 4.3% (28/651), and the most frequent SPMs were haematological malignancies. In conclusion, the frequency of SPMs in our cohort of heavily pretreated patients receiving CAR-T was relatively low and consistent with previous studies.

NR1H3 (LXRα) is associated with pro-inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b-cell lymphoma.

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3high patients displayed longer survival compared with NR1H3low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes.

Clinical features of respiratory syncytial virus bronchiolitis in an infant: rapid and fatal brain involvement.

BACKGROUND: Respiratory Syncytial Virus (RSV) infection is a significant cause of bronchiolitis and pneumonia, mostly responsible for hospitalization and infant death worldwide. However, in recent years the importance of extrapulmonary RSV manifestations, especially at neurological level, have become evident. Seizures, lethargy, ataxia and status epilepticus are suggestive of brain involvement, but also in their absence a direct neurological damage RSV-related need to be evaluated. CASE PRESENTATION: A 40-day old male infant was admitted to the Emergency Department with severe bronchiolitis and dyspnea. The patient was reported to be coughing for a week with a vomiting episode in the previous two days. The nasopharyngeal swab confirmed the diagnosis of RSV infection and blood gas test showed hypoxemia and respiratory acidosis. For these reasons, the patient was provided with oxygen therapy. A few hours later, after an initial improvement in clinical parameters, a worsening of respiratory dynamics occurred and the patient was prepared for endotracheal intubation, but in the meantime death occurred. During all the observation period in the Emergency Room, no signs of neuropathological damage were evident. Post mortem examination showed lungs congestion with alveolar atelectasis and white matter degradation with severe edema at brain level. Microbiological analysis performed on autoptic samples confirmed the presence of RSV genome in tracheobronchial aspirate, meningeal swabs, pericardic and abdominal fluids, lung and brain biopsies. CONCLUSIONS: RSV is usually associated with respiratory diseases, however, as reported by an increasingly number of studies, the systemic dissemination of virus during severe disease can lead to a sudden infant death. The clinical picture herein reported showed a severe bronchiolitis resulting in a fatal and underestimated cerebral involvement due to RSV neurotropic behaviour and underline the need for clinicians to pay more attention to neurological involvement of RSV infection, even in absence of cerebral damage evidence.

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial.

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13-year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P<0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma. (Registered at clinicaltrials.gov identifier: 00435955).

Cocirculation of Hajj and non-Hajj strains among serogroup W meningococci in Italy, 2000 to 2016.

In Italy, B and C are the predominant serogroups among meningococci causing invasive diseases. Nevertheless, in the period from 2013 to 2016, an increase in serogroup W Neisseria meningitidis (MenW) was observed. This study intends to define the main characteristics of 63 MenW isolates responsible of invasive meningococcal disease (IMD) in Italy from 2000 to 2016. We performed whole genome sequencing on bacterial isolates or single gene sequencing on culture-negative samples to evaluate molecular heterogeneity. Our main finding was the cocirculation of the Hajj and the South American sublineages belonging to MenW/clonal complex (cc)11, which gradually surpassed the MenW/cc22 in Italy. All MenW/cc11 isolates were fully susceptible to cefotaxime, ceftriaxone, ciprofloxacin, penicillin G and rifampicin. We identified the full-length NadA protein variant 2/3, present in all the MenW/cc11. We also identified the fHbp variant 1, which we found exclusively in the MenW/cc11/Hajj sublineage. Concern about the epidemic potential of MenW/cc11 has increased worldwide since the year 2000. Continued surveillance, supported by genomic characterisation, allows high-resolution tracking of pathogen dissemination and the detection of epidemic-associated strains.

Rapid Identification of Microorganisms from Positive Blood Culture by MALDI-TOF MS After Short-Term Incubation on Solid Medium.

Matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is a useful tool for rapid identification of microorganisms. Unfortunately, its direct application to positive blood culture is still lacking standardized procedures. In this study, we evaluated an easy- and rapid-to-perform protocol for MALDI-TOF MS direct identification of microorganisms from positive blood culture after a short-term incubation on solid medium. This protocol was used to evaluate direct identification of microorganisms from 162 positive monomicrobial blood cultures; at different incubation times (3, 5, 24 h), MALDI-TOF MS assay was performed from the growing microorganism patina. Overall, MALDI-TOF MS concordance with conventional methods at species level was 60.5, 80.2, and 93.8% at 3, 5, and 24 h, respectively. Considering only bacteria, the identification performances at species level were 64.1, 85.0, and 94.1% at 3, 5, and 24 h, respectively. This protocol applied to a commercially available MS typing system may represent, a fast and powerful diagnostic tool for pathogen direct identification and for a promptly and pathogen-driven antimicrobial therapy in selected cases.

Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013.

In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p < 0.001). Overall 81 serogroup Y IMD cases were identified, with a median age of 18 years, ranging from three months to 84 years. Of the 81 respective patient samples, 56 were further subject to molecular typing. The sequence type (ST)-23 complex (clonal complex (cc)23) was predominant among serogroup Y meningococci (54/56 samples), and included nine different STs. Presumably, ST-23 was the founding genotype, with all the other STs presenting as single-locus variants. All cc23 isolates analysed harboured mutations in the lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.

A multi-center real-life prospective study of axicabtagene ciloleucel versus tisagenlecleucel toxicity and outcomes in Large B-Cell Lymphomas.

This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 relapsed-refractory large B-cell lymphoma patients with baseline characteristics matched by Stabilized Inverse Propensity-Score Weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs 89.3%, p=0.0017) and neurotoxicity (9.9% vs 32.2%, p<0.0001), but also superior progression-free survival (PFS) at one year (46.5% vs 34.1%, p=0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs 22.7%, p=0.0059). Differences in overall survival (OS) and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, p<0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy balancing bridging, safety and efficacy considerations for individual patients.

Axicabtagene ciloleucel treatment is more effective in primary mediastinal large B-cell lymphomas than in diffuse large B-cell lymphomas: the Italian CART-SIE study.

Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190). Median follow-up time for infused patients was 12.17 months (IQR 5.53,22.73). The overall (complete + partial) response rate (ORR,CR + PR) after bridging was 41% for PMBCL and 28% for other LBCL, p = 0.0102. Thirty days ORR was 78% (53/68) with 50% (34) CR in PMBCL, and 75% (141/187) with 53% (100) CR in other LBCL, p = 0.5457. Ninety days ORR was 69% (45/65) with 65% (42) CR in PMBCL, and 54% (87/162) with 47% (76) CR in other LBCL; progressive disease was 21% in PMBCL and 45% in other LBCL, p = 0.0336. Twelve months progression-free survival was 62% (95% CI: 51-75) in PMBCL versus 48% (95% CI: 41-57) in other LBCL, p = 0.0386. Twelve months overall survival was 86% (95% CI: 78-95) in PMBCL versus 71% (95% CI: 64-79) in other LBCL, p = 0.0034. All grade cytokine release syndrome was 88% (228/260); all grade neurotoxicity was 34% (88/260), with 6% of fatal events in PMBCL. Non-relapse mortality was 3%. In conclusion, PMBCLs achieved significantly better response and survival rates than other LBCLs.

Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study.

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product. The phase 2 TRANSCEND FL study evaluated liso-cel in patients with R/R FL, including 2L patients who all had POD24 from diagnosis after treatment with anti-CD20 antibody and alkylator ≤6 months of FL diagnosis and/or met modified Groupe d'Etude des Lymphomes Folliculaires criteria. Primary/key secondary endpoints were independent review committee-assessed overall response rate (ORR)/complete response (CR) rate. At data cutoff, 130 patients had received liso-cel (median follow-up, 18.9 months). Primary/key secondary endpoints were met. In third-line or later FL (n = 101), ORR was 97% (95% confidence interval (CI): 91.6‒99.4), and CR rate was 94% (95% CI: 87.5‒97.8). In 2L FL (n = 23), ORR was 96% (95% CI: 78.1‒99.9); all responders achieved CR. Cytokine release syndrome occurred in 58% of patients (grade ≥3, 1%); neurological events occurred in 15% of patients (grade ≥3, 2%). Liso-cel demonstrated efficacy and safety in patients with R/R FL, including high-risk 2L FL. ClinicalTrials.gov identifier: NCT04245839 .

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

The lymphocyte to monocyte ratio improves the IPI-risk definition of diffuse large B-cell lymphoma when rituximab is added to chemotherapy.

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B-cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver-operating characteristic (ROC) analysis and Harrell's C-statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab-containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab-based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab-supplemented chemotherapy programs, an LMR value of <2.6 was found in most of the primary refractory patients (75%) which proved as the best cutoff to predict both response and survival (P = 0.018). Finally, multivariate analysis and Harrell's C-statistics confirmed the IPI-independent role of LMR on survival (P = 0.0000). In conclusion, LMR is a potent predictor of clinical response and survival in DLBCL treated with rituximab-containing chemotherapy.

Performance Evaluation of BD Phoenix and MicroScan WalkAway Plus for Determination of Fosfomycin Susceptibility in Enterobacterales.

BACKGROUND: Fosfomycin is an old bactericidal drug that has gained increasing interest in the last decade for its potential use in multi-drug resistant gram-negative infections. However, evidence on fosfomycin susceptibility testing reports a poor correlation between commercial methods vs. reference agar dilution (AD) for Enterobacterales (EB). The study aimed at assessing the performance of two automated systems for the determination of fosfomycin susceptibility in EB clinical isolates. METHODS: Fosfomycin susceptibility testing results of two collections of 100 non-duplicate clinical EB strains obtained using two different platforms (BD Phoenix and MicroScan WalkAway Plus) were compared with those obtained by AD. Categorical agreement (CA), major error (ME) and very major error (VME) rates were calculated. RESULTS: BD Phoenix exhibited a 6.9% rate of false-resistant results and achieved a CA of 69%, whereas MicroScan WalkAway Plus achieved 3.7% of false-resistant results and 72% of CA. Both automated systems showed poor detection of resistant isolates, with 49.1% and 56.2% of false-susceptible results for BD Phoenix and Microscan WalkAway Plus, respectively. CONCLUSIONS: Overall, agar dilution remains the most suitable method for routine laboratory antimicrobial susceptibility testing of fosfomycin on Enterobacterales strains, given the poor performance of automated systems. The application of both automated systems, in the clinical laboratories reporting of fosfomycin, should be reviewed in light of the accuracy results falling below the acceptable threshold.

Seven Years of Culture Collection of Neisseria gonorrhoeae: Antimicrobial Resistance and Molecular Epidemiology.

The emergence of Neisseria gonorrhoeae isolates displaying resistance to antimicrobials, in particular to ceftriaxone monotherapy or ceftriaxone plus azithromycin, represents a global public health concern. This study aimed to analyze the trend of antimicrobial resistance in a 7-year isolate collection retrospective analysis in Italy. Molecular typing on a subsample of gonococci was also included. A total of 1,810 culture-positive gonorrhea cases, collected from 2013 to 2019, were investigated by antimicrobial susceptibility, using gradient diffusion method, and by the N. gonorrhoeae multiantigen sequence typing (NG-MAST). The majority of infections occurred among men with urogenital infections and 57.9% of male patients were men who have sex with men. Overall, the cefixime resistance remained stable during the time. An increase of azithromycin resistance was observed until 2018 (26.5%) with a slight decrease in the last year. In 2019, gonococci showing azithromycin minimum inhibitory concentration above the EUCAST epidemiological cutoff value (ECOFF) accounted for 9.9%. Ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae (PPNG) percentages increased reaching 79.1% and 18.7% in 2019, respectively. The most common sequence types identified were 5,441, 1,407, 6,360, and 5,624. The predominant genogroup (G) was the 1,407; moreover, a new genogroup G13070 was also detected. A variation in the antimicrobial resistance rates and high genetic variability were observed in this study. The main phenotypic and genotypic characteristics of N. gonorrhoeae isolates were described to monitor the spread of drug-resistant gonorrhea.

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy.

Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD). Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy. Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022. Exposures: Routine 4CMenB vaccination, per regional vaccination programs. Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact. Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose. Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.

Comparison of Three Different Commercial Methods for Fosfomycin Susceptibility Testing in Pseudomonas aeruginosa.

The lack of internationally approved breakpoint and a handy susceptibility testing reduces fosfomycin usefulness against Pseudomonas aeruginosa. Previous works defined low or moderate agreement between commercial methods and the reference method (agar dilution [AD]). In particular, data lack about testing against P. aeruginosa. We compared disk diffusion (DD), E-test (ET), and automated broth microdilution (BMD) to AD by testing 150 P. aeruginosa isolates. We obtained better categorical agreement (CA) for DD and ET for minimal inhibitory concentration >128 mg/L (84.7% and 92.7%, respectively), but with high very major error (VME). BMD had the lowest VME rate (2/42), but with 64% CA and 52/108 major errors. We cannot define a method comparable to AD. Larger studies, as well as the definition of a breakpoint value are needed for fosfomycin against P. aeruginosa.

Evaluation of Meningococcal Serogroup C Bactericidal Antibodies after Primary Vaccination: A Multicentre Study, Italy.

Here, we evaluated over time in different cohorts of children vaccinated against serogroup C Neisseria meningitidis, the presence of antibodies with neutralizing activity. A total of 348 sera samples of enrolled children by year since vaccination (<1 year- up to 5 years), starting from February 2016 to December 2017, were collected in three collaborating centers. Meningococcal serogroup C (MenC) antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA) following standard operating procedures. The cut-off of rSBA titer ≥ 8 is considered the correlate of protection. We observed a significantly declining of bactericidal rSBA titers by 23% every year, for every 1-year from vaccination (Adjusted PR = 0.77, 95% CI: 0.71−0.84). The proportions of children with bactericidal antibodies, immunized with the meningococcal serogroup C conjugate (MCC) vaccine, declined from 67.7% (95% CI: 48.6−83.3%) one year after vaccination, to 36.7% (95% CI: 19.9−56.1%) five years after vaccination (chi-square for linear trend, p < 0.001). Children vaccinated with the tetravalent meningococcal serogroup ACWY vaccine resulted in a high proportion of bactericidal rSBA MenC titer ≥ 1:8 (90.6%, 95% CI: 79.3−96.9%) after a mean time of seven months. Overall, the results provide some evidences on the evaluation of meningococcal serogroup C bactericidal antibodies after primary vaccination.

Comparison of Different Chemical and Mechanical Modalities for Implant Surface Decontamination: Activity against Biofilm and Influence on Cellular Regrowth-An In Vitro Study.

Objectives: The aim of this in vitro study was to compare the efficacy of chemical and mechanical methods for decontamination of titanium dental implant surfaces previously infected with polymicrobial biofilms in a model simulating a peri-implant defect. Furthermore, the effect of each decontamination protocol on MG-63 osteoblast-like cells morphology and adhesion to the treated implants was assessed. Background: Peri-implantitis is a growing issue in dentistry, and evidence about implant surface decontamination procedures is lacking and inconclusive. Methods: A total of 40 previously biofilm-contaminated implants were placed into a custom-made model simulating a peri-implant defect and randomly assigned to five treatment groups: (C) control (no treatment); (AW) air abrasion without any powder; (ESC) air abrasion with powder of erythritol, amorphous silica, and 0.3% chlorhexidine; (HBX) decontamination with a sulfonic/sulfuric acid solution in gel; and (HBX + ESC) a combination of HBX and ESC. Microbiological analysis was performed on five implants per treatment group, and the residual viable bacterial load measured in log 10 CFU/mL was counted for each bacterial strain and for the total number of colonies. The remaining three implants per group and three noncontaminated (NC) implants were used to assess surface biocompatibility using a scanning electron microscope and a backscattered electron microscope after seeding with MG-63 cells. Results: A significant decontaminant effect was achieved using HBX or HBX + ESC, while no differences were observed among other groups. The percentage of implant surface covered by adherent MG-63 cells was influenced by the treatment method. Progressive increases in covered surfaces were observed in groups C, AW, ESC, HBX, HBX + ESC, and NC. Conclusions: A combination of mechanical and chemical decontamination may provide more predictable results than mechanical cleaning alone.

Activity of ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol and comparators against Gram-negative organisms causing bloodstream infections in Northern Italy (2019-2021): emergence of complex resistance phenotypes.

Herein we assessed the frequency of Gram-negative organisms causing bloodstream infections and activity spectrum of ceftolozane-tazobactam (CTZ), ceftazidime-avibactam (CZA), meropenem-vaborbactam (MEV), cefiderocol (CFDC) and comparators. Overall, 1605 Gram-negative isolates were consecutively collected during 2019-2021. Enterobacterales represented more than 75% and exhibited >90% susceptibility to CZA (97%), amikacin (91.8%) and meropenem (90.6%). ESBL-producing Enterobacterales isolates showed high rates of susceptibility towards CZA (100%), carbapenems (89.1-100%) and CTZ (84.9-95.1%). MEV displayed the highest activity against KPC-producing Enterobacterales (MIC50/90, 0.75/4 mg/L; 92.9% susceptible) followed by CZA (MIC50/90, ≤2/>8 mg/L; 89.3% susceptible), CFDC (MIC50/90, 0.25/4 mg/L, 87.5% susceptible) and colistin (MIC50/90, ≤2/4 mg/L, 83.9% susceptible). High proportions of P. aeruginosa isolates were susceptible to colistin (97.8%), CZA (97.2%), CTZ (96.1%) and amikacin (94.5%). CFDC showed potent activity against Acinetobacter baumannii (MIC50/90, 0.5/1 mg/L; 97.2% susceptible), multi-drug resistant P. aeruginosa (MIC50/90, 0.25/1 mg/L; 96% susceptible), and Stenotrophomonas maltophilia (MIC50/90, 0.12/0.25 mg/L; 100% susceptible).